Biomedical subjects

Tobias Peikert

Publications and source records attributed to Tobias Peikert.

4 recordsLinked to original sources

PubMed2006

Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes apoptosis.

A variety of melanoma antigen A (MAGE-A) genes are commonly detected in non-small cell lung cancers. Their biological function is not well characterized but may involve the regulation of apoptosis and cell cycle progression. We hypothesized that MAGE-A4 is involved in the regulation of apoptosis. To investigate this, expression of MAGE-A was evaluated. MAGE-A4 was expressed in 48% of non-small cell lung carcinomas. Ninety percent of lung carcinomas expressing MAGE-A4 were classified as squamous cell carcinomas and 10% were adenocarcinomas. Tumor-free surrounding lung tissue was negative for MAGE-A4. A molecular clone of MAGE-A4 derived from human lung cancer was stably expressed in human embryonic kidney cells (293 cells) to evaluate effects on cell death. Overexpression of MAGE-A4 increased apoptosis as measured by the apoptotic index (P < 0.0001) and caspase-3 activity (P < 0.002). Exposure to 25 micromol/L etoposide, a chemotherapeutic agent, increased the apoptotic effect (P < 0.0001). Furthermore, we show that MAGE-A4 silencing using a small interfering RNA approach results in decreased caspase-3 activity in the squamous cell lung cancer cell line H1703 by 58% (P = 0.0027) and by 24% (P = 0.028) in 293/MAGE-A4 cells. These findings suggest that MAGE-A4 expression may promote tumor cell death, sensitize malignancies to apoptotic stimuli, such as chemotherapeutic agents, and therefore may represent a tumor suppressor protein.

Aged↗

PubMed2005

A novel capture-ELISA for detection of anti-neutrophil cytoplasmic antibodies (ANCA) based on c-myc peptide recognition in carboxy-terminally tagged recombinant neutrophil serine proteases.

Testing for antineutrophil cytoplasmic antibodies (ANCA) reacting with proteinase 3 (PR3) is part of the routine diagnostic evaluation of patients with small vessel vasculitis. For PR3-ANCA detection, capture ELISAs are reported to be superior to direct ELISAs. Standard capture ELISAs, in which PR3 is anchored by anti-PR3 monoclonal antibodies (moAB), have two potential disadvantages. First, the capturing moAB may compete for epitopes recognized by some PR3-ANCA, causing occasional false-negative results. Second, the capture of recombinant PR3 mutant molecules becomes unpredictable as modifications of specific conformational epitopes may not only affect the binding of PR3-ANCA, but also the affinity of the capturing anti-PR3 moAB. Here, we describe a new capture ELISA, and its application for PR3-ANCA detection. This new assay is based on the standardized capture of a variety of different carboxy-terminally c-myc tagged recombinant ANCA target antigens using anti-c-myc coated ELISA plates. Antigen used include c-myc tagged human rPR3 variants (mature and pro-form conformations), mouse mature rPR3 and human recombinant neutrophil elastase. This new anti-c-myc-capture ELISA for PR3-ANCA detection has an intra- and inter-assay coefficient of variation of 3.6% to 7.7%, and 15.8% to 18.4%, respectively. The analytical sensitivity and specificity for PR3-ANCA positive serum samples were 93% and 100%, respectively when rPR3 with mature conformation was used as target antigen, and 83% and 100% when the pro-enzyme conformation was employed. In conclusion, this new anti-c-myc capture ELISA compares favorably to our standard capture ELISA for PR3-ANCA detection, enables the unified capture of different ANCA target antigens through binding to a c-myc tag, and allows capture of rPR3 mutants necessary for PR3-ANCA epitope mapping studies.

Animals↗

PubMed2005

Safety, diagnostic yield, and therapeutic implications of flexible bronchoscopy in patients with febrile neutropenia and pulmonary infiltrates.

OBJECTIVE: To evaluate the safety, diagnostic yield, and therapeutic implications of flexible bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy in patients with febrile neutropenia and pulmonary infiltrates. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all patients with neutropenic fever and pulmonary infiltrates evaluated by flexible bronchoscopy and BAL between January and December 2002 at the Mayo Clinic in Rochester, Minn. Appropriate demographic, clinical, microbiological, and histological data and procedure-related complications were summarized. Therapeutic decisions implemented based on Information obtained by bronchoscopy, and 28-day mortality were determined. RESULTS: Thirty-five patients with febrile neutropenia and associated pulmonary infiltrates were identified. Flexible bronchoscopy, including 35 BALs and 9 transbronchial biopsies, was performed safely (3 complications). The diagnostic yield of BAL was 49%. Sputum analysis was underused (only 34%) but complementary to BAL. The combined diagnostic yield of BAL and sputum analysis was 63%. Transbronchial biopsy provided additional information to BAL and sputum analysis In only 1 patient and did not substantially increase the combined diagnostic yield. The most common diagnoses identified were fungal pneumonias (15/35 [43%]) and diffuse alveolar hemorrhage (5/35 [14%]). Bronchoscopic findings resulted in management changes in 51% of patients. The 28-day mortality rate was 26% and was highest in patients who required mechanical ventilatory assistance before bronchoscopy. CONCLUSION: The favorable safety record, good diagnostic yield, and frequent therapeutic implications support the routine use of BAL for the evaluation of pulmonary inflitrates in neutropenic patients. Bronchoalveolar lavage should be combined with the analysis of several sputum specimens. Transbronchial biopsy did only change the management of 1 patient.

Anti-Bacterial Agents↗

PubMed2005

Catamenial pneumothorax.

Catamenial pneumothorax is defined as spontaneous pneumothorax occurring within 72 hours before or after onset of menstruation. Although catamenial pneumothorax is the most common clinical manifestation of intrathoracic endometriosis, this latter condition is not universally identified in women with catamenial pneumothorax and cannot fully explain the recurrent and cyclical episodes of pneumothorax. Therefore, the etiology of this syndrome is unknown, although many theories have been proposed to explain it. We describe a 37-year-old woman with recurrent episodes of spontaneous right-sided pneumothorax and chest pain that occurred close to her menstrual periods. The patient's condition did not abate after initial surgical exploration with abrasive mechanical pleurodesis or after hormonal suppressive therapy at an institution elsewhere. The patient was referred to our institution for further evaluation. A second surgical inspection of the pleural cavity and diaphragm disclosed the presence of multiple diaphragmatic fenestrations that were closed surgically at that time. Postoperatively, the patient discontinued hormonal suppressive therapy, and menstrual cycles became regular. Six months after surgery, the patient remains asymptomatic with no evidence of recurrence of pneumothorax. This case supports recent reports that diaphragmatic defects are often present in patients with catamenial pneumothorax. Surgical exploration to inspect the diaphragm and to close all Identified defects should be performed in patients who continue to experience pneumothorax despite effective hormonal suppression.

Adult↗